T-lymphocytes comprise an indispensable component of the adaptive immune response, yet certain autoimmune, infectious, parasitic, and neoplastic diseases subvert adaptive immunity by specifically misdirecting T-helper cell polarity. A common mechanism of immune subversion is the aberrant recruitment of a Th2 dominant response that directly promotes B-cell antibody production and interferes with direct effector cell cytotoxicity. In contrast, a Th1 dominant response evokes cytotoxic effects with the production of IFNγ and IL2, which contribute to effector cell-based immune surveillance. Clearance of certain intracellular bacterial pathogens such as Listeria and parasites such as Leishmania, as well as tumor immune surveillance, hinge upon the capacity to elicit robust Th1 and CD8 T-cell responses.
Interleukin-2 Inducible Kinase (ITK) is a T-cell dominant member of the TEC-kinase family that drives proximal T-cell receptor (TCR) signaling. Upon TCR ligation in Th1 and CD8 T-cells, ITK and redundant resting lymphocyte kinase (RLK or TXK) activate PLCγ, launching a signaling cascade that includes the NFAT, NFκB, and MAPK pathways resulting in cellular activation, cytokine release, and rapid proliferation. ITK plays a supportive yet dispensable role to RLK in Th1 polarized and CD8 effector cells, but is indispensable for signaling in Th2 polarized T-cells.